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Ashkenazi Parkinson’s disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries

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Abstract

The LRRK2 G2019S mutation is a major genetic determinant of Parkinson’s disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived ∼1,830 (95% CI 1,560–2,160) years ago, around the second century, after the second Jewish Diaspora.

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References

  1. de Rijk MC, Launer LJ, Berger K et al (2000) Prevalence of Parkinson’s disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54:S21–S23

    PubMed  Google Scholar 

  2. Eriksen JL, Wszolek Z, Petrucelli L (2005) Molecular pathogenesis of Parkinson disease. Arch Neurol 62:353–357. doi:10.1001/archneur.62.3.353

    Article  PubMed  Google Scholar 

  3. Hernandez DG, Paisan-Ruiz C, McInerney-Leo A et al (2005) Clinical and positron emission tomography of Parkinson’s disease caused by LRRK2. Ann Neurol 57:453–456. doi:10.1002/ana.20401

    Article  CAS  PubMed  Google Scholar 

  4. Healy DG, Falchi M, O’Sullivan SS et al (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol 7:583–590. doi:10.1016/S1474-4422(08)70117-0

    Article  CAS  PubMed  Google Scholar 

  5. Lesage S, Durr A, Tazir M et al (2006) LRRK2 G2019S as a cause of Parkinson’s disease in North African Arabs. N Engl J Med 354:422–423. doi:10.1056/NEJMc055540

    Article  CAS  PubMed  Google Scholar 

  6. Ozelius LJ, Senthil G, Saunders-Pullman R et al (2006) LRRK2 G2019S as a cause of Parkinson’s disease in Ashkenazi Jews. N Engl J Med 354:424–425. doi:10.1056/NEJMc055509

    Article  CAS  PubMed  Google Scholar 

  7. Orr-Urtreger A, Shifrin C, Rozovski U et al (2007) The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect? Neurology 69:1595–1602. doi:10.1212/01.wnl.0000277637.33328.d8

    Article  CAS  PubMed  Google Scholar 

  8. Goldwurm S, Di Fonzo A, Simons EJ et al (2005) The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson’s disease and originates from a common ancestor. J Med Genet 42:e65. doi:10.1136/jmg.2005.035568

    Article  CAS  PubMed  Google Scholar 

  9. Kachergus J, Mata IF, Hulihan M et al (2005) Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet 76:672–680. doi:10.1086/429256

    Article  CAS  PubMed  Google Scholar 

  10. Lesage S, Leutenegger AL, Ibanez P et al (2005) LRRK2 haplotype analyses in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century. Am J Hum Genet 77:330–332. doi:10.1086/432422

    Article  CAS  PubMed  Google Scholar 

  11. Warren L, Gibson R, Ishihara L et al (2008) A founding LRRK2 haplotype shared by Tunisian, US, European and Middle Eastern families with Parkinson’s disease. Parkinsonism Relat Disord 14:77–80. doi:10.1016/j.parkreldis.2007.02.001

    Article  CAS  PubMed  Google Scholar 

  12. Zabetian CP, Hutter CM, Yearout D et al (2006) LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: evidence of two distinct founding events beginning two millennia ago. Am J Hum Genet 79:752–758. doi:10.1086/508025

    Article  CAS  PubMed  Google Scholar 

  13. Stephens M, Scheet P (2005) Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation. Am J Hum Genet 76:449–462. doi:10.1086/428594

    Article  CAS  PubMed  Google Scholar 

  14. Genin E, Tullio-Pelet A, Begeot F et al (2004) Estimating the age of rare disease mutations: the example of Triple-A syndrome. J Med Genet 41:445–449. doi:10.1136/jmg.2003.017962

    Article  CAS  PubMed  Google Scholar 

  15. Fenner JN (2005) Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. Am J Phys Anthropol 128:415–423. doi:10.1002/ajpa.20188

    Article  PubMed  Google Scholar 

  16. Tremblay M, Vezina H (2000) New estimates of intergenerational time intervals for the calculation of age and origins of mutations. Am J Hum Genet 66:651–658. doi:10.1086/302770

    Article  CAS  PubMed  Google Scholar 

  17. Struewing JP, Abeliovich D, Peretz T et al (1995) The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 11:198–200. doi:10.1038/ng1095-198

    Article  CAS  PubMed  Google Scholar 

  18. Bar-Sade RB, Theodor L, Gak E et al (1997) Could the 185delAG BRCA1 mutation be an ancient Jewish mutation? Eur J Hum Genet 5:413–416

    CAS  PubMed  Google Scholar 

  19. Bar-Sade RB, Kruglikova A, Modan B et al (1998) The 185delAG BRCA1 mutation originated before the dispersion of Jews in the diaspora and is not limited to Ashkenazim. Hum Mol Genet 7:801–805. doi:10.1093/hmg/7.5.801

    Article  CAS  PubMed  Google Scholar 

  20. Goodman RM MAe, (1979) Genetic diseases among Ashkenazi Jews. New York: Raven Press

  21. Hulihan MM, Ishihara-Paul L, Kachergus J et al (2008) LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol 7:591–594. doi:10.1016/S1474-4422(08)70116-9

    Article  CAS  PubMed  Google Scholar 

  22. Bras J, Guerreiro R, Ribeiro M et al (2008) Analysis of Parkinson disease patients from Portugal for mutations in SNCA, PRKN, PINK1 and LRRK2. BMC Neurol 8:1. doi:10.1186/1471-2377-8-1

    Article  PubMed  Google Scholar 

  23. Ferreira JJ, Guedes LC, Rosa MM et al (2007) High prevalence of LRRK2 mutations in familial and sporadic Parkinson’s disease in Portugal. Mov Disord 22:1194–1201. doi:10.1002/mds.21525

    Article  PubMed  Google Scholar 

  24. Bras JM, Guerreiro RJ, Ribeiro MH et al (2005) G2019S dardarin substitution is a common cause of Parkinson’s disease in a Portuguese cohort. Mov Disord 20:1653–1655. doi:10.1002/mds.20682

    Article  PubMed  Google Scholar 

  25. Benamer HT (2008) The ancestry of LRRK2 Gly2019Ser parkinsonism. Lancet Neurol 7:769–770. doi:10.1016/S1474-4422(08)70178-9 author reply 770-771

    Article  PubMed  Google Scholar 

  26. Zabetian CP, Morino H, Ujike H et al (2006) Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease. Neurology 67:697–699. doi:10.1212/01.wnl.0000227732.37801.d4

    Article  CAS  PubMed  Google Scholar 

  27. Ross OA, Spanaki C, Griffith A et al (2008) Haplotype analysis of Lrrk2 R1441H carriers with parkinsonism. Parkinsonism Relat Disord . doi:10.1016/j.parkreldis.2008.09.001

    Google Scholar 

  28. Haugarvoll K, Rademakers R, Kachergus JM et al (2008) Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease. Neurology 70:1456–1460. doi:10.1212/01.wnl.0000304044.22253.03

    Article  CAS  PubMed  Google Scholar 

  29. Mata IF, Cosentino C, Marca V et al (2008) LRRK2 mutations in patients with Parkinson’s disease from Peru and Uruguay. Parkinsonism Relat Disord . doi:10.1016/j.parkreldis.2008.09.002

    PubMed  Google Scholar 

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Acknowledgments

The assistance of Dr. Helena Yagev-More is gratefully acknowledged. This work was supported by grants from National Parkinson Foundation, Miami, USA, Tel Aviv Sourasky Medical Center Grant of Excellence, and Wolfson and Kahn Foundations.

Declaration

The experiments were complied with the current laws of Israel, the country in which they were performed.

Author information

Authors and Affiliations

  1. Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 64239, Israel

    Anat Bar-Shira & Avi Orr-Urtreger

  2. Movement Disorders Unit Parkinson Center, Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 64239, Israel

    Nir Giladi

  3. The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Nir Giladi & Avi Orr-Urtreger

  4. Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA

    Carolyn M. Hutter

  5. Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington School of Medicine, Seattle, WA, USA

    Cyrus P. Zabetian

  6. Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA

    Cyrus P. Zabetian

Authors
  1. Anat Bar-Shira
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  2. Carolyn M. Hutter
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  3. Nir Giladi
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  4. Cyrus P. Zabetian
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  5. Avi Orr-Urtreger
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Corresponding author

Correspondence to Avi Orr-Urtreger.

Electronic Supplementary Material

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Supplementary Table. LRRK2 G2019S Haplotypes (XLS 43 KB)

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Bar-Shira, A., Hutter, C.M., Giladi, N. et al. Ashkenazi Parkinson’s disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries. Neurogenetics 10, 355–358 (2009). https://doi.org/10.1007/s10048-009-0186-0

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  • DOI: https://doi.org/10.1007/s10048-009-0186-0

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